Theiler's virus infection induces TLR3-dependent upregulation of TLR2 critical for proinflammatory cytokine production.
Theiler's virus infection induces TLR3-dependent upregulation of TLR2 critical for proinflammatory cytokine production.
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DOI：
10.1002/glia.20843
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发表时间：
2009-08-15
期刊：
影响因子：
6.2
通讯作者：
Kim, Byung S.
中科院分区：
文献类型：
--
作者：
So, Eui Young;Kim, Byung S.
Theiler小鼠脑脊髓炎病毒（TMEV）感染直接诱导许多促炎基因，包括I型干扰素（IFN）和多种细胞因子基因。这些病毒诱导的细胞因子是发生TMEV诱导的脱髓鞘疾病的关键因素。我们以前曾报道，细胞因子基因的主要激活信号是通过TLR 3介导的。在这项研究中，我们描述了TLR 2通过TLR 3信号上调，并协同参与TMEV感染后IL-6，IL-1β，CCL 2和CCL 5基因的表达。这些基因的表达在TLR 2缺陷型和TLR 3缺陷型原代星形胶质细胞中均显著受损。然而，I型IFN的诱导不受原代细胞中TLR 2缺陷的影响。TMEV感染导致TLR 2介导的NF-κB活化，但不导致IRF 3或IRF 7活化，这对I型IFN的产生至关重要。更重要的是，TLR 3是TMEV诱导的原代星形胶质细胞中TLR 2早期上调所必需的，导致产生TLR 2依赖性细胞因子如IL-6。有趣的是，通过TLR 2/3依赖性信号产生的可溶性因子似乎与下游细胞因子的产生部分相关。这些结果表明，TMEV利用TLR 3诱导的TLR 2来诱导炎性细胞因子，这对免疫介导的脱髓鞘疾病的发展至关重要。
Theiler's murine encephalomyelitis virus (TMEV) infection directly induces many proinflammatory genes, including type I interferon (IFN) and a variety of cytokine genes. These virus-induced cytokines are a critical factor in developing TMEV-induced demyelinating disease. We have previously reported that the major activation signal for the cytokine genes is mediated via TLR3. In this study, we describe that TLR2 is upregulated via TLR3 signal and cooperatively participates in the expression of IL-6, IL-1β, CCL2, and CCL5 genes following TMEV infection. The expression of these genes was significantly impaired in both TLR2-deficient and TLR3-deficient primary astrocytes. However, the induction of type I IFNs was not affected by TLR2-deficiency in the primary cells. TMEV infection led to TLR2-mediated NF-κB activation, but not IRF3 or IRF7 activation critical for type I IFN production. More importantly, TLR3 was required for TMEV-induced early TLR2 upregulation in primary astrocytes leading to the production of TLR2-dependent cytokines such as IL-6. Interestingly, soluble factor(s) produced via TLR2/3-dependent signals appears to be partially associated with the downstream cytokine production. These results indicate that TMEV utilizes TLR3-induced TLR2 to induce inflammatory cytokines, which are critical to the development of immune-mediated demyelinating disease.
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DOI：
10.1179/096805104225006516
发表时间：
2004-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Kurt-Jones, EA;Sandor, F;Finberg, RW
通讯作者：
Finberg, RW
影响因子：
3.1
作者：
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通讯作者：
Giambartolomei, Guillermo H.
影响因子：
6.2
作者：
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通讯作者：
Miller, Stephen D.
影响因子：
4.8
作者：
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通讯作者：
Calderwood, SK
DOI：
10.1006/meth.1996.0123
发表时间：
1996-01-01
期刊：
Methods (Orlando)
影响因子：
--
作者：
Dal Canto, Mauro C.;Kim, Byung S.;Melvold, Roger W.
通讯作者：
Melvold, Roger W.